The trp repressor of E. coli (TR) regulates the expression of at least four operons involved in aromatic amino acid biosynthesis in response to intracellular levels of L-tryptophan. This regulation involves thermodynamic coupling of multiple equilibria, arising not only from protein - ligand and protein - DNA interactions, but protein - protein interactions and protein folding processes as well. The relative in vivo importance of each of these interactions on repressor activity can be probed by the in vitro physical analysis of these processes for super-repressor mutants of the repressor. The structural basis for the coupling of ligand binding to DNA binding, that is, the basis for the allosteric regulation of DNA binding by L- tryptophan, has been proposed to involve coupling of partial folding of the aporepressor upon ligand (as well as DNA) binding, rather than only the conformational differences observed by comparison of the unligated and ligand bound crystal structures. Direct calorimetric determination of the thermodynamic parameters for ligand binding to various mutants of TR will provide insight into the nature and extent of this coupling, improving our understanding of the energetics of allosteric control in this system, and of transcriptional regulation in general.